The candidate, Katherine E. Gregory, PhD, RN, aims to become an independent clinical investigator who will lead her field in an innovative program of patient-oriented research. Dr. Gregory's program of research will generate new models of disease pathogenesis and prediction using cutting-edge biochemical analysis (i.e. microbiome) and bioinformatic prediction strategies (i.e. metabolomics). As part of her research training and experience to date, she has identified clinical predictors of necrotizing enterocolitis (NEC) in premature infants. This work has extended knowledge of antecedents of NEC well beyond prematurity and demographics. Dr. Gregory will remain focused on NEC, one of the major unsolved problems of neonatal care, the most common gastrointestinal emergency experienced by premature infants, and the leading reason for aberrant nutrition, growth and neurodevelopment in premature infants. New paradigms are needed to understand NEC etiology and pathobiology, which will aid in our prediction of this and other diseases. The central hypothesis of the research proposed is that NEC may be predicted in a population of extremely low gestational age neonates using non-serum based biologic sample (i.e. urine and stool). The use of urine for biomarker assays and stool for biochemical prediction techniques has the advantage of a noninvasive approach that would not deplete the low gestational age infant of an already limited blood volume. Dr. Gregory will train in the scientific methods related to the human microbiome of gastrointestinal disease pathogenesis under the mentorship of W. Allan Walker, MD. She will work under the mentorship of Bruce Kristal, PhD in conducting the metabolomic and bioinformatic analyses for the purpose of disease prediction. Finally, Dr. Gregory will be mentored by Linda Van Marter, MD, MPH in the clinical setting where she will collect biologic sample, develop a specimen bank for future analysis, and conduct an epidemiologic investigation of clinical factors related to NEC. This mentorship team has been selected for a diversity of research expertise in areas including gastrointestinal disease, nutrition, microbiome analysis, metabolomics, and cutting-edge neonatal research. In sum, the candidate will work with seasoned mentors in a world-class research environment. She will be successful in her research and training aims. RELEVANCE: Despite advances in neonatal intensive care and significant gains in premature infant survival, necrotizing enterocolitis remains one of the most significant complications of premature birth. Disease prediction, a priority area in patient-oriented research, will revolutionize how we take care of patients and improve human health. New paradigms are needed to understand the pathogenesis of NEC, which will aid in our ability to predict this disease and in turn improve care for premature infants.